Nalmefene

The FDA approved Opvee in 2023 for health care and community use, naming harm reduction groups and emergency responders among those it should reach.⁷ The European Union authorised Selincro in 2013 to help adults with alcohol dependence who drink heavily cut down.²

Nalmefene at a glance

In the US, nalmefene reverses opioid overdoses

Nalmefene reverses slowed breathing, heavy sedation and low blood pressure caused by opioids, and it has no opioid effect of its own.³ It is not expected to have any effect in someone who hasn't taken opioids.³

How fast it works. Both devices were tested in volunteers whose breathing was slowed in a lab with remifentanil (Opvee) or fentanyl (Zurnai). Breathing began to recover 2.5 to 5 minutes after the dose and was back to normal within 5 to 15 minutes.^3,8

How it is given. Opvee is one spray in one nostril. Zurnai is pressed against the outer thigh and held for 3 seconds. After either, call 911, turn the person on their side and follow the package steps; more doses may be needed.^3,8 The Zurnai label warns that comparing nalmefene products milligram for milligram "may be misleading."⁸

Buprenorphine overdoses. Reversal of buprenorphine (the opioid in Suboxone) may be incomplete and need repeat doses, because buprenorphine lets go of the receptor slowly.³

Pregnancy. The Opvee label says overdose treatment should not be withheld over concerns about the fetus.³

Nalmefene lasts longer than naloxone; claims it works better rest on a model

All three nalmefene labels state that, in pharmacodynamic studies, nalmefene injection acted longer than naloxone injection at fully reversing doses.^3,8,9 The blood half-life is 11.4 hours for the Opvee spray, 9.07 hours for Zurnai and 10.8 hours (give or take 5.2) for the vial.^3,8,9 Naloxone's shorter timing is covered on naltrexone vs naloxone.

The Opvee label says nalmefene lasts "as long as most opioids," yet breathing can slow again after an apparently good response.³ An overdose of a long-acting opioid such as methadone may slow breathing for a long time.⁹

The Laffont study was funded by Indivior, which now sells Opvee, and 3 of its 5 authors are Indivior employees.^1,11 In the Kaplan trial, 75% of people who tested positive for opioids had also taken other sedating drugs.¹⁵

Longer action can mean longer withdrawal

In someone physically dependent on opioids, nalmefene can set off withdrawal with vomiting, diarrhea, sweating, a fast heartbeat, fever and restlessness.^3,8 The Laffont authors, whose study favours nalmefene, write that its longer half-life and tighter grip on opioid receptors "have the potential risk to produce a more severe and longer precipitated withdrawal."¹¹ In a review of 27 case-report papers on long-acting blockers, 4 involved nalmefene, and symptoms took 3 to 48 hours to settle with treatment.¹⁶ More on timing by drug is on precipitated withdrawal.

Sudden reversal has also caused seizures, dangerous heart rhythms, fluid in the lungs and cardiac arrest, mostly in people with heart disease or taking drugs with similar heart effects.³ Taking more opioids to push through the block can lead to a fatal overdose.³

In hospital, the vial label tells clinicians to start with a small test dose when they suspect opioid dependence and to give no more than it takes to restore normal breathing.⁹ The sprays and auto-injectors deliver a fixed dose.^3,8

Whether underdosing is a bigger risk than withdrawal "remains a matter of debate," according to the Laffont authors.¹¹

In Europe, nalmefene is taken as needed to cut drinking

Selincro is an 18 mg nalmefene tablet from Lundbeck. It is for adults with alcohol dependence who drink more than 60 g of alcohol a day (men) or 40 g (women), have no physical withdrawal symptoms and don't need immediate detox. It is used only together with counselling.² People take one tablet as needed, ideally 1 to 2 hours before they are likely to start drinking. It does not stop alcohol from making you drunk, and it must not be used by people taking opioids.²

UK guidance (NICE TA325, 2014) recommends nalmefene for people at a high drinking-risk level, with continuous psychosocial support, started only if they are still drinking at that level 2 weeks after their first assessment.¹⁷

A later analysis pooled the 667 people from both trials who were still drinking at a high-risk level when treatment began. In that group, nalmefene cut 3.2 more heavy-drinking days a month and 14.3 g more a day than placebo.¹⁸ Side effects were more common on nalmefene in both trials; dropouts because of them were more common in ESENSE 1 and similar in ESENSE 2.^12,13 In a pooled analysis of 1,276 patients from two nalmefene trials, people took the tablet on about half of study days.¹⁹

A 2016 meta-analysis with an author from Lundbeck, which markets Selincro, found a standardized effect of −0.20 on heavy-drinking days.^2,20 A 2018 network meta-analysis of 32 trials put nalmefene's effect on total drinking at −0.19 and found no high-grade evidence for any of the five drugs it covered.²¹

Nalmefene vs naltrexone for alcohol

The labels describe nalmefene as a "6-methylene analogue of naltrexone," and both drugs block opioid receptors.^3,14 The 2016 meta-analysis adds that nalmefene partly activates the kappa opioid receptor.²⁰

Availability. Every US nalmefene product is a spray or an injection, and the current labels cover overdose and opioid reversal only.^1,3,8,9 Naltrexone tablets are FDA-approved for alcohol dependence at 50 mg once daily.¹⁴ Taking naltrexone only before drinking, the idea behind the Sinclair Method, is the closest US match to how Selincro is used, and it is off-label.¹⁴

Head to head. The 32-trial review found no study that compared the drugs directly. In trials of people who were still drinking, it saw an effect on total drinking for nalmefene and none for naltrexone, though 26 of the 32 trials were at risk of incomplete outcome data.²¹ Naltrexone's wider evidence, including trials aimed at stopping, is summarized on does naltrexone work and the alcohol use disorder guide.

Same opioid rule. Neither drug can be combined with opioid use: Selincro must not be taken with opioid medicines, and starting naltrexone with opioids still in the body can set off precipitated withdrawal.^2,14

How we checked

• Read in full on October 17, 2026: the Opvee, Zurnai and nalmefene injection labels; Drugs@FDA records; the FDA's Opvee announcement; NICE TA325; the Laffont 2024 full text, including its funding statement.
• Read as summaries: EMA's Selincro page and the other studies.
• Study types are named in the table.^{1-3,7-9,11,17}